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Biomedical subjects

E McFarland

Publications and source records attributed to E McFarland.

At least 19 recordsLinked to original sources
PubMed2002

The injury risk associated with pes planus in athletes.

Despite the common prophylactic use of rigid orthotics in athletes with flat feet to prevent subsequent injury, there is little scientific data in the literature examining the relationship between pes planus and athletic injuries to the lower extremity. The current prospective study was undertaken to establish what relationship, if any, exists between foot morphology and subsequent lower extremity injury. A total of 196 subjects were enrolled in the study, of which 143 (73%) were male and 53 (27%) were female. Forty-two percent of the participants (83) engaged in contact sports. There were a total of 227 episodes of injury involving the lower extremity. Logistic regression using contact sports, gender, and all of the different foot contact areas that were measured at the beginning of the study was undertaken. Although gender and participation in contact sports was predictive of some lower extremity injuries, the existence of pes planus as measured by medial midfoot contact area as a percentage of total contact area was not a risk factor for any injury of the lower extremity. This study shows that in an athletic population that is representative of collegiate athletics, the existence of flat footedness does not predispose to subsequent lower extremity injury. The routine prophylactic use of orthotics in flat-footed athletes to prevent future injury may therefore not be justified based on the data available.

Ankle Injuries↗
PubMed2000

Electroporation of antibodies, DNA, and other macromolecules into cells: a highly efficient method.

While antibodies are a major extracellular tool of the highest specificity to answer important biomedical questions, the improvements in electroporation discussed below may make it feasible to also use antibodies as an intracellular deletion tool to study (a) viruses inside the cell, (b) cancer cells, (c) signal transduction, (d) genetics, (e) metabolism, and (f) other structures and mechanisms. Already, others have succeeded in depositing macromolecules, including antibodies (Abs), and nucleic acids inside cells, using many techniques, including electroporation (EP). However, EP has limitations that have precluded its widespread use, particularly its high kill rate for cells and the low percentage of cells that are able to incorporate macromolecules. If these limitations could be overcome for Abs and nucleic acids, then it would be practical to use them as highly specific probes for intracellular molecules. In our experiments using EP, we were able to largely prevent lethality for cells during EP by employing a commercially available cold-storage solution for organ transplants containing high K(+) and Mg(++) (ViaSpan, Belzer UW cold-storage solution, DuPont Pharmaceuticals). This solution decreased cell death after standard EP by an average of 50% for a number of cell lines. Viability of WISH cells after EP approached 100%. In transfection studies, ViaSpan medium strongly increased both P3HR1 cell survival as well as the total number of cells transfected with DNA for green fluorescent protein (GFP). In additional experiments with Abs, we were able to strongly increase the percent of cells that incorporated Ab by using two serial EPs. This enhanced the intracellular protection by Abs against viruses in Vero cells from 64% to a maximum of 98%. We were able to further simplify the EP technique by using unpurified antiserum in place of purified IgG. Thus, this EP technique offers multiple advantages: simplicity, high cell viability, high effectiveness, high specificity, rapid action, usefulness with adherent or non-adherent cells, and no requirement for purification of antibodies from antiserum.

Animals↗
PubMed2000

Lymphoproliferative responses to recombinant HIV-1 envelope antigens in neonates and infants receiving gp120 vaccines. AIDS Clinical Trial Group 230 Collaborators.

Children of mothers infected with human immunodeficiency virus type 1 (HIV-1) were immunized at birth and at 1, 3, and 5 months with 1 of 3 doses of recombinant gp120 vaccines prepared from SF-2 or MN strains of HIV-1. A total of 126 children were not infected; 21 received adjuvant only. Vaccine recipients developed lymphoproliferative responses on >/=2 occasions, responding more often to homologous HIV-1 antigens than did adjuvant recipients (56% vs. 14%; P<.001). Responses were appreciated after 2 immunizations and were maintained for >84 weeks after the last immunization. An accelerated immunization schedule (birth, 2 weeks, 2 months, and 5 months) with the lowest dose of the SF-2 vaccine produced responses in all 11 vaccinees by 4 weeks. Responses to heterologous envelope antigens were also detected. Immune responses to vaccination are achievable at an age when some infection (perinatal or breast milk exposure related) may be prevented.

AIDS Vaccines↗
PubMed1999

Immunizations for the immunocompromised child.

Although immunocompromised children are unlikely to have optimal immune responses to vaccines, some will benefit from immunization. They should receive inactivated vaccines that are routinely recommended for immunocompetent children plus pneumococcal and influenza immunizations. Live viral and bacterial vaccines are contraindicated with the exception of MMR. It may be given to children infected with HIV who do not have severe immunosuppression. The timing of immunizations is generally the same for immunocompromised and normal children. However, the MMR schedule in children infected with HIV is accelerated, with 2 doses given 1 month apart. Susceptible children whose immunosuppression is related to a temporary condition should be vaccinated after immune dysfunction has resolved. The question of revacination for children infected with HIV who are receiving effective antiretroviral therapy is under investigation, but no specific recommendations are currently available.

Child↗
PubMed1996

T2 relaxation times of hypervascular and non-hypervascular liver lesions: do hypervascular lesions mimic haemangiomas on heavily T2-weighted MR images?

AIM: To correlate the T2 relaxation times of liver lesions with their vascularity at angiography and to determine whether hypervascular lesions have similar signal intensity to haemangiomas on heavily T2-weighted MR images. PATIENTS AND METHODS: Thirty-four patients with histologically proven malignant liver lesions had both angiography and T2W (SE 3000/80,160) MR imaging (1.5 T) of the liver. Angiographically, the lesions were hypervascular in 15 and non-hypervascular in 19 patients. Fifteen additional patients with proven haemangioma also had MR imaging during the same time period. The T2 relaxation time of a representative lesion was calculated for each patient and the results compared. RESULTS: The mean T2 time for hypervascular lesions was 76 +/- 21 ms compared with 79 +/- 18 ms for non-hypervascular lesions (P = 0.61). The mean T2 relaxation time for haemangiomas was significantly longer than either group: 147 +/- 46 ms (P = 0.0001). CONCLUSION: The T2 relaxation times of hypervascular and non-hypervascular liver lesions are similar and are significantly shorter than those of haemangiomas. Therefore, hypervascular lesions should not mimic haemangiomas on heavily T2-weighted images.

Carcinoma, Hepatocellular↗
PubMed1989

Brain creatine phosphate and creatine kinase in mice fed an analogue of creatine.

Brain phosphocreatine (PCr) concentration and creatine kinase (CK) activity have been studied by 31P nuclear magnetic resonance (NMR) spectroscopy in mice fed an analogue of creatine, beta-guanidinopropionic acid (GPA). The phosphorylated analogue (GPAP), which almost completely replaces PCr in skeletal muscle, is a poor substrate for CK. Mice, which received GPA in food (2%) and water (0.5%) for up to 9 months beginning at 35 days of age, were normal in appearance and activity. Maximal brain GPAP concentration, reached after two weeks of feedings, was approximately equal to the concentration of PCr. The concentration of PCr decreased at least 20% relative to that of the nucleoside triphosphates. When GPA feedings were stopped, GPAP disappeared in about 20 days from skeletal muscle, but only after 40-50 days from brain. Steady-state NMR saturation transfer studies showed a markedly reduced chemical exchange rate from PCr to ATP in brains of GPA-fed mice. These results suggest a compartmentation of brain PCr. The GPA-accessible PCr compartment has a slow rate of PCr turnover compared to skeletal muscle. The slow reaction rate of the GPA-inaccessible PCr as a CK substrate is consistent with the hypothesis that this residual PCr is the same compartment which is stable in hypoxic or seizing animals.

Adenosine Triphosphate↗
PubMed1988

Estimation of tumor oxygenation and metabolic rate using 31P MRS: correlation of longitudinal relaxation with tumor growth rate and DNA synthesis.

31P MRS longitudinal relaxation times (T1) were determined for C3H murine fibrosarcomas (FSaII), and mammary carcinomas (MCaIV). Tumors were implanted in the foot dorsum, and were 100-300 mm3 in volume. T1s were repeated after the animal was allowed to breathe 100% oxygen for 30 min and then again 36-48 hr following 30 Gy. The spectrum were obtained using an 8.5 T spectrometer with a 8 cm bore and a 1.4 cm single turn antenna coil. The 31P relaxation times for untreated tumors in air breathing animals were: 3.78 sec for phosphomonoesters, 4.37 sec for inorganic phosphate (Pi), 2.73 sec for phosphocreatine, 1.37 sec for gamma ATP, 1.14 sec for alpha ATP, and 1.18 sec for beta ATP. The Pi T1s were 4.37 and 4.70 sec in control and irradiated tumors in air breathing animals. Respiration of oxygen for 30 min reduced the T1s to 3.02 and 2.62 sec in control and irradiated tumors respectively. The Pi T1 of an anoxic tumor, determined on an in situ tumor 60 min after death was 5.93 sec. The oxygen breathing induced decrease in the T1 of Pi is unlikely to have been caused by the paramagnetic properties of oxygen alone, and suggests a component of increased magnetization transfer secondary to the ATPase reaction. Oxygen breathing following 30 Gy, resulted in a decreased growth time (800 mm3 endpoint) and an increased proportion of cells in S-phase. These results support the hypothesis that the decrease in Pi T1 measured with oxygen breathing is a measure of tumor oxygen tension and metabolic rate, and suggests that T1 measurement may indirectly predict tumor growth rate and DNA synthesis.

Animals↗
PubMed1987

Unknown phosphate compounds in tail muscle of intact conscious newts by 31P NMR.

Unknown phosphate resonances at 0 and -21.6 ppm have been identified in 31P NMR spectra of tail muscle of unanesthetized newts which do not correspond to known phosphate-bearing compounds in skeletal muscle cells. The concentrations of both unknowns decrease markedly during muscular activity and severe hypoxia (conditions associated with decreased intracellular pH and increased cellular levels of inorganic phosphate). The unknown at 0 ppm increases in concentration with imposition of moderate hypoxia. Our data suggest that these unknowns may be liable storage compounds for a high energy phosphate bond, and are involved in newt skeletal muscle phosphogen metabolism.

Adenosine Triphosphate↗
PubMed1987

Effects of oxygen on the metabolism of murine tumors using in vivo phosphorus-31 NMR.

The effect of 100% inspired oxygen on in vivo tumor metabolism was examined using phosphorus-31 (31P) NMR spectroscopy. Isotransplants of two murine tumor histologies, designated MCaIV (C3H mammary adenocarcinoma) and FSaII (C3H fibrosarcoma), were used in syngeneic mice. Tumor volumes ranged from 30 to 1,800 mm3. Both tumor histologies are known to have a high hypoxic cell fraction when tumor volumes exceed 250 mm3. 31P nuclear magnetic resonance (NMR) spectra were obtained at 145.587 MHz, and the signal was detected using a 1.4 cm diameter, single loop coil designed to localize the signal from only the tumor. Spectral parameters for optimal signal-to-noise ratio (SNR) included a 60 degrees pulse and a 2-second recycle delay. Tumors were implanted in the hindfoot dorsum to assure that all detected mobile phosphates were of tumor origin. Phosphocreatine/inorganic phosphate (PCr/Pi) ratios of large tumors (greater than 250 mm3) were reduced compared with small tumors (less than 250 mm3) of the same histology. The increased PCr/Pi response to 100% inspired oxygen was greater for large tumors and for tumors with lower baseline PCr/Pi ratios. When host animals were given 10% oxygen for respiration, there was an increase in Pi and a decrease in both PCr and ATP. The response to 10% oxygen was observed in both large and small tumors of both tumor histologies studied. Resting skeletal muscle exhibited no alteration in the NMR spectrum during either 100 or 10% oxygen breathing. We conclude that the fractional increase in PCr/Pi ratio that occurs after 100% oxygen breathing is a sensitive, noninvasive method of detecting tumor hypoxia.

Animals↗
PubMed1986

Tumor size dependent changes in a murine fibrosarcoma: use of in vivo 31P NMR for non-invasive evaluation of tumor metabolic status.

Tumor tissue contains viable hypoxic regions that are radioresistant and often chemoresistant and may therefore be responsible for some treatment failures. A subject of general interest has been the development of non-invasive means of monitoring tissue oxygen. Pulse Fourier transform 31P NMR spectroscopy can be used to estimate intracellular nucleotide triphosphates (NTP), phosphocreatinine (PCr), inorganic phosphate (Pi) and pH. We have obtained 31P NMR spectra as an indirect estimate of tissue oxygen and metabolic status in a C3H mouse fibrosarcoma FSaII. Sequential spectra were studied during tumor growth in a cohort of animals and peak area ratios for several metabolites were computed digitally by computer. During growth, tumors showed a progressive loss of PCr with increasing Pi, and most tumors greater than 250 mm3 in volume had little or no measurable PCr. The smallest tumors (38 mm3 average volume) had PCr/Pi ratios of 1.03 +/- .24, whereas tumors 250 mm3 or more had an average PCr/Pi ratio of 0.15 +/- .04. Similarly derived NTP/Pi ratios decreased with tumor size, but this change was not significant (p = .17). Radiobiologic hypoxic cell fractions were estimated using the radiation dose required to control tumor in 50% of animals (TCD50) or by the lung colony technique. Tumors less than 100 mm3 had a hypoxic cell fraction of 4% (TCD50) while tumors 250 mm3 had a 40% hypoxic cell fraction (lung colony assay). These hypoxic fraction determinations correlated well with the depletion of PCr and decline in NTP/Pi ratios seen at 250 mm3 tumor volumes. Tumor spectral changes with acute ischemia were studied after ligation of the tumor bearing limb and were similar to changes seen with tumor growth. PCr was lost within 7 minutes, with concurrent increase in Pi and loss of NTP. Complete loss of all high energy phosphates occurred by 40 minutes of occlusion. In vivo tumor 31P NMR spectroscopy can be used to estimate tissue metabolic status and may be useful in non-invasive prediction of hypoxic cell fraction, reoxygenation, and radiation treatment response.

Animals↗
PubMed1985

A genetically determined murine model of infantile polycystic kidney disease.

We have evaluated a congenic strain of mice with congenital polycystic kidney disease in which the disease process appears to closely resemble human infantile polycystic kidney disease. Cysts formed first in the proximal tubules of the nephron and appeared, by light microscopy, to be preceded by vacuolization of the cells. These spaces, as seen by electron microscopy, occurred between adjacent cells. The pancreas was severely involved with reduction of both exocrine and endocrine elements. Cyst formation in the liver was minimal. Serum samples evaluated for urea nitrogen and creatinine were significantly elevated in affected mice. Serum glucose was within normal limits.

Animals↗
PubMed1985

Surface coil MR imaging of abdominal viscera. Part I. Theory, technique, and initial results.

Prototype surface coil magnetic resonance (MR) images were obtained from phantoms and 42 subjects at 0.6 T to assess the feasibility of imaging relatively deep abdominal structures. Surface coil images demonstrated a two- to fourfold improvement in signal-to-noise ratio (SNR) when compared with whole-body coil images with the same resolution elements. This improvement in SNR allowed us to obtain images with thinner sections, higher in-plane resolution, or, alternatively, a decrease in image time. Compared with body images, surface coil images demonstrated greater anatomic detail and reduction in motion artifacts. Despite the limited field of view in very large patients, the use of surface coils improves the diagnostic capability of MR imaging of the abdomen.

Abdomen↗
PubMed1985

The hematopoietic stem cells of alpha-thalassemic mice.

The alpha-thalassemic mouse has a hereditary microcytic anemia, almost certainly has a shortened RBC life span, and is a potential candidate for cell replacement therapy. In a routine study of bone marrow repopulating capacity using hemoglobin as a cell marker, normal donor marrow cells, but not alpha-thalassemic donor marrow cells, completely replaced the host cells. Further analysis showed that at least 30 times more alpha-thalassemic cells were required to outcompete normal donor cells injected simultaneously. The results were more extreme then expected and suggested a defect in a stem cell population as well as in the RBCs. Evidence that the multipotent and erythroid-committed stem cells in alpha-thalassemic mice are not decreased was shown by CFU-S and CFU-E assays. The combined results indicate that the deletion expresses itself most conspicuously in the RBC population. Tests were also performed to analyze repopulation kinetics in the Hbath-J/+ mice. In unirradiated alpha-thalassemic hosts, the hemoglobin from a normal donor persisted but did not replace the host hemoglobin. Sublethally irradiated alpha-thalassemic hosts, on the other hand, were easily repopulated with normal cells. We conclude that the alpha-thalassemic mouse is a good model for cell replacement therapy.

Animals↗
PubMed1984

Isoelectric focusing--polynucleotide/polyacrylamide-gel electrophoresis. A technique to separate and characterize nuclease activities.

Individual native nuclease activities from human leucocytes are separated by using two-dimensional gel electrophoresis in an apparatus that allows the simultaneous running of 28 gels. Proteins are separated by isoelectric focusing in a disc gel, followed by electrophoresis into a slab gel containing DNA. Protein denaturants are avoided in the second dimension by the use of a running pH well above the optimal pH for DNAase (deoxyribonuclease) activity. Electrophoresed gels are incubated in appropriate buffers to activate nuclease activity. After staining for intact DNA, the positions of active enzymes, unobscured by the presence of other proteins, are revealed as colourless spots in a reddish-purple field. The technique is easy to use and is sensitive to 50pg of DNAase I. Versatility is provided by the use of either acidic or basic electrophoresis running buffers and by the use of specific gel incubation conditions to reveal different sets of enzyme activities. Two DNAases active at pH 7.4 in the presence of Mg2+ and Ca2+, and sixteen DNAases active at acidic pH and not requiring metals, are detected. Treatment of the human enzymes with specific glycosidases reveals that many of the human DNAases are glycoproteins containing negatively charged moieties and may be derived from modification of parent activities.

Deoxyribonucleases↗
PubMed1984

Development of the embryonic murine kidney in normal and congenital polycystic kidney disease: characterization of a proximal tubular degenerative process as the first observable light microscopic defect.

The current report presents findings from a comparative histological and histochemical investigation of murine congenital polycystic kidney disease. The studies revealed that the morphological changes are initiated in the developing proximal tubules of the nephron; differences from control sections first become evident at 16 days' gestation. As the disease progresses, obvious changes include hyperplasia and dilation of the tubule, cellular vacuolization, and alterations in the apical cell brush border. Included among the latter changes are decreases in enzyme (alkaline phosphatase) staining and decreases in glycoprotein staining (periodic acid Schiff). All such changes continue until the kidney is markedly cystic and apical cell cytochemical staining is absent. Some cellular vacuolization, assumed to be a normal developmental event, is also seen within the same segment of the proximal tubule at 17 days' gestation through the 1st postnatal day. Dilation of the collecting duct is noted to be a later or secondary change evident after the initial onset of the disease.

Animals↗